#2022GM/Q09
#2022BSQ-NOV/Q18
#2020BSQ-NOV/Q56
"Paraneoplastic syndromes refer to groupings of symptoms that occur in patients with malignant neoplasms that cannot be readily explained by local invasion or distant metastasis of the tumor, or the elaboration of hormones indigenous to the tissue of origin of the neoplasm. Paraneoplastic syndromes occur in 10–15% of cancer patients."
Definition of paraneoplastic syndromes in Robbin's Basic Pathology:
They can be triggered by an abnormal immune response to the tumour, or by substances secreted by the neoplasm itself.
The term nonbacterial thrombotic endocarditis (NBTE), or marantic endocarditis, refers to a spectrum of lesions ranging from microscopic aggregates of platelets to large vegetations on previously undamaged heart valves (most often aortic and mitral) in the absence of a bloodstream bacterial infection. Source
The cancers most commonly associated with paraneoplastic syndromes (PNS) are
- anti-Hu antibody indicates the presence of a small cell lung cancer
- the anti-Yo antibody, the presence of an ovarian or breast cancer. Source
Hypercoagulability
Trousseau syndrome - migratory thrombophlebitis occuring in association with malignancy.
Nephrotic syndrome - commonest cause is membranous nephropathy.
HPO - hypertrophic pulmonary osteoarthropathy (clubbing of fingers and toes)
Inflammatory myopathies - [[2021 General Medicine July#Polymyositis and dermatomyositis|DM and PM]]
The most common biologically active substance secreted from carcinoid tumors is 5-HT (serotonin), a vasoactive peptide whose biosynthesis is accomplished nearly exclusively by the enterochromaffin cells. Synthesized from the amino acid tryptophan, the release of 5-HT into the systemic circulation can cause the classic symptoms of the carcinoid syndrome, which include diarrhea, episodic flushing, bronchoconstriction, and eventual right-sided valvular heart disease
[[Hypertension in pregnancy#Paraneoplastic syndromes associated with lung cancer]]
- It is a common ==multisystemic== ==inflammatory== disease that begins more frequently between 20 and 60 years of age and represents the most frequent of all interstitial lung diseases.
[!TIP] Bilateral Hilar lymphadenopathy SCaLP
Incidence is increasing.
Symptoms:
#2020BSQ-NOV/Q51
[!INFO] Changes after MI: A summary of the changes given in Robbins.
- Upto about 4 hours, it looks like nothing happened.
- Then the infarct slowly mottles and darken upto about 24 hours.
- From then on, coagulative necoris changes are seen.
- Phagocytosis of the coagulative necrotic area starts after about 3 days and continues upto 7 days.
- Laying down of granulation tissue begins around 7 days and intensifies upto 14 days.
- Laid down granulation tissue begins to turn fibrotic by about 14 days (2 weeks).
- Scar formation is complege by 8 weeks, the scar has formed.
#2020BSQ-NOV/Q56
Benign tumours are of no clinical significance as benign cortical papillary adenomas occur in about 40% of adults.
Renal cancers are mainly of 3 types
Symptoms:
Symptoms are may be flu like; about 15% develop lymphadenopathy (painless) (usually head and neck) . Symptoms resolve spontaneously in a few weeks to months;
Pyrimethamine is an antiparasitic prescription medicine
Congenital toxoplasmosis;
- Live cysts: Antihelminthing treatment must be combined with steroid which penetrates the BBB (Dexamethasone) to lessen the inflammatory response elicited following death of the parasite.
A good detailed Source
[!INFO] Exerpt from the summary of the article above:
- Granuloma macrophages can undergo different types of specialized differentiation.
- Multiple additional types of cells can be recruited in the granuloma and influence its structure and function.
- Granulomas can form in response to large and small particles, which can be infectious agents or nonliving objects.
- Many granulomas occur in the context of inflammatory and autoimmune diseases in the absence of a known antigenic trigger.
Granuloma formation is a histologic pattern of chronic inflammation.
The pattern of inflammation can be classified in many ways. (necrotizin or not / Suppurative or not etc.)
This corresponds to the features of the granuloma after 'maturation'.
The prototypes are
| Crohn's disease | Occasional non caseating granulomas with dense fibrous infiltrate |
Their membranes begin to interdigitate and the nuclei swell.
Naked granulomas - only sparse lymphocytic infiltrate at margin of granuloma; is a typical sarcoid lesions.
Suppurative granulomas - have neutrophils at the center.
Tuberculoid granuloma - caseous necrosis
Foreign body granulomas
Necrbiotic - contains altered collagen in the center. Also has acellular substances in the center.
Treatment:
[!INFO]
Is pulmonary fibrosis due to drugs dose or time dependant?
Classification of vasculitides
Good article on pulmonary vaculitis
#2021SBR-JULQ16
Patient it always > 50 years old; sudden onset pain and stiffness (but not weakness) of limb girdles / proximal muscles, associated with raised inflammatory markers.
ALP and gamma GT may be elevated.
Giant cell arteritis is seen in 30% of cases.
Treatment: 15mg prednisilone mane : improvement is significant in 24 to 48 hours.
#2022SBR Q8
#2021GM-JUL/Q17
[!INFO] The most common idiopathic systemic vasculitis.
Females >>> males (3:1)
Always over 50;
Commonest in scandinavians.
Inflammatory, granulomatous, arteritis or large cerebral arteries.
Histology: Cellular infiltrates of CD4+ cells, macrophages and giant cells.
Patient has usually had past or current PMR. (age always > 50)
Presentations: Severe headaches, scalp / temple tenderness.
IX: NCNC anaemia and elevated ESR.
Treatment should commence immediately.
Giving steroids is essential, since it can prevent vision loss due to ophthalmic artery ischemia.
Steroid should be given in much higher doses than PMR.
High dose steroid therapy can cause osteoporosis.
Definitive Dx : temporal artery biopsy. Patchy lesions -> >1cm needs to be examined.
Only half will have [[Miscellaneous respiratory medicine#Polymyalgia rheumatica|polymyalgia rheumatica]]
Almost never occurs in young people (below 50 years old)
Liver biochemistry may be abnormal
Affects the largest vessels in the body: the aorta and it's branches.
Mostly affects women of childbearing age!
AKA pulseless disease or aortic arch syndrome.
[!INFO]
Complete obstruction of the left common carotid
(eg, bruit, especially carotid; blood pressure difference of extremities, difference in pulse volume, claudication, hypertension)
Steroids are the mainstay.
Diagnosis: MR angiograms.
Post prandial abdominal pain, diarrhoea, GI haemorrhage.
The immune complex mediated medium vessel vasculitis.
[!INFO] Pathology
Segmental, transmural, necrotizing inflammation.
Characteristically, all stages of inflammation are present in different vessels / same vessel.
Robbin williams : As a middle aged man, playing Peter PAN!
1/3 of patients have chronic hepatitis B infection.
Occurs in middle aged men; associated with severe systemic symptoms.
Fibrinoid necrosis of vessel walls -> thrombosis and infarction.
Probably immune complex mediated (as it's sometimes associated Hep B).
Involves ==small arteries within the organs==.
Frequency of involvement : Kidney > heart > liver > GI tract
4. Renal: haematuria and proteinuria.
5. Coronary arteritis causing MI.
6. Liver
7. Bowel ischemia -> acute abdominal pain, necrosis and bleeding
9. Mononeuritis mulitiplex - vaso vasorum infarctions
10. Skin - subcutaneous haemorrhage and gangrene
11. Somehow, lungs aren't involved.
Treatment: Corticosteroids +/- azathioprine.
Predominantly occurs in children < 5 years old.
Systemic medium vessel arteritis. The main problems are due to coronary ischemia caused by coronary artery vasculitis leading to
Pathology: transumural inflammation seen but not as severe as PAN.
Treatment:
Steroids to now show benefit!
Single dose of Iv-Ig followed by aspirin.
[!TIP] Mnemonic
Small vessel vasculitedes are divided into
ANCA-associated vasculitis (AAV) - paucity of vessel wall immunoglobulin and presence of ANCA.
3. MPA (Microscopic polyangitis) - no other name.
Immune complex SVV - prominence of vessel wall immunoglobulin.
[!INFO] Features common to small vessels vasculitides
Of vasculitidies, small vessel vasculitides commonly affect the lungs.
Small vessel vasculitides are ANCA positive.
Frequent kidney involvement
mnemonic: G for greenwich ; GPA is in europe.
[!INFO] Types of ANCA antibodies
It was found that the serum of patients with vasculitis would stain neutrophils in one of two pattersn:
- Perinuclear - this serum has p-ANCA antibodies
- Cytoplasmic - this serum has c-ANCA antibodies.
C-ANCA stains neutrophil proteinsase 3 (PR3 ANCA = cANCA)
P-ANCA stains neurtrophil myeloperoxidase (MPO ANCA = pANCA)
c in C3PO and 3 is also in C3POpANCA - MPA and EGPA
cANCA - GPA
" c " in c-ANCA looks like " G " in GPA.
should be suspected in any patient who presents with
constitutional symptoms along with
clinical evidence of glomerulonephritis,
upper or lower respiratory tract involvement, or multiple mononeuropathy.
Fortunately for US, MPA and GPA are similar diseases but with some differences.
They present in older adults.
most commonly affected organs are upper and lower respiratory tract and kidneys.
URT - Otitis (even hearing loss), bloody nasal discharge, crusting, oral or nasal ulcers.
LRT - hoarseness, dry cough, pleuritic chest pain, life threatening haemoptysis.
Kidney - rapidly proliferative glomerulonephritis. -> nephritic picture
Skin - purpura of lower extremeties.
GPA and MPA are similar but differ in the following:
| GPA | MPA |
|---|---|
| Granuloma + ("granulomatosis") | Granuloma (-) |
| Relapse risk is much higher | Lower relapse risk |
| Acute kidney involvement (necrosis and crescents) | Chronic lesions (tubulointerstitial fibrosis / glomerulosclerosis |
| PR3-ANCA type | MPO-ANCA |
| GPA - europe | MPA - East asia |
[!TIP] Otitis, sinusitis, cough and glomerulonephritis and an older adult
GPA is the commonest ANCA associated vasculitis.
It is a granulomatous disease. The granulomas are not well formed like those in TB or sarcoidosis.
However, the granulomas can obstruct blood vessels and are necrotizing granulomas.
Lungs: Liquefactive necrosis seen in granulomas.
Kidneys: Focal necrotizing glomerulonephritis with crescents and thrombosis.
Affects older adults.
c-ANCA positive.
Upper respiratory tract : sinusitis , ears -> Otitis media.
Glomerulonephritis is present.
Diffuse alveolar haemorrhage and life threatening haemoptysis occurs in upto 45%.
Cough, dysponoea, pleuritic chest pain.
Staining pattern characteristic of each ANCA type
c-ANCA - diffuse staining
p-ANCA - perinuclear staining
Presents in early adulthood.
Eosinophilia+
Allergic rhinitis and asthma that's difficult to control.
p-ANCA positive. (=MPO ANCA)
Systemic vasculitis develops later:
Responds well to steroids.